Congenital dyserythropoietic anemias (CDAs) are a heterogeneous group of disorders characterized by anemia, ineffective erythropoiesis with specific morphological alterations of erythroid precursors in the marrow, and iron overload.
Although rare, uncovering the molecular basis of CDA has helped unravel novel aspects of the cell biology of erythropoiesis.
Three classical types of CDA have been distinguished. However, some patients with phenotype of CDA do not fit into any of these categories.
Clinical and Laboratory Features
The condition presents in infancy or adolescence.
Autosomal recessive inheritance is caused by mutations in the CDAN1 gene, encoding codanin-1, a cell cycle–regulated protein involved in the histone assembly; homozygosity is often associated with consanguinity. In a number of patients, only one or no CDAN1 mutated allele is identified; other causative genes, such as C15ORF41, are suspected.
Moderately severe macrocytic anemia (approximately 9.0 g/dL) occurs.
Hepatomegaly and cholelithiasis are common.
Splenomegaly increases with age.
Specific morphologic findings of CDA type I are summarized in Table 7–1 and exemplified in Figure 7–1.
Dysmorphic skeletal features may be present, typically affecting hands and feet. Less common are small stature, almond-shaped blue eyes, hypertelorism, and micrognathia.
TABLE 7–1CARDINAL FEATURES OF TYPES I, II, AND III CONGENITAL DYSERYTHROPOIETIC ANEMIAS (CDAS) |Favorite Table|Download (.pdf) TABLE 7–1 CARDINAL FEATURES OF TYPES I, II, AND III CONGENITAL DYSERYTHROPOIETIC ANEMIAS (CDAS)
|CDA Type ||Light Microscopy ||Electron Microscopy ||Serology ||Inheritance |
|I ||Most erythroid cells abnormal: double nuclei, internuclear chromatin bridges (Fig. 7–1) ||Widened nuclear pores, spongy appearance of the heterochromatin, invasion by the cytoplasm containing various organelles ||No serologic abnormalities ||Autosomal recessive |
|II ||Mature stage erythroblasts with two or more nuclei, lobulated nuclei, karyorrhexis, pseudo-Gaucher cells (Fig. 7–1) ||Endoplasmic reticulum cisternae lining the inner surface of the red cell plasma membrane ||Cells containing the HEMPAS antigen are lysed by 30% of acidified normal sera; strong reactivity with anti-“i” autoantibodies ||Autosomal recessive |
|III ||Giant erythroblasts, up to 50 μm in diameter, with up to 12 nuclei, basophilic stippling ||Clefts and blebs within nuclear areas, some iron-filled mitochondria, autophagic vacuoles and myelin figures in the cytoplasm ||No clearly defined abnormalities ||Autosomal dominant (not all cases) |
Light microscopy of marrow. A. Congenital dyserythropoietic anemia type I. The internuclear unusually long chromatin bridge is marked by an arrow. B. Congenital dyserythropoietic anemia type II. The two arrows point to binucleate erythroblasts, characteristic of this type. (Used with permission from Dr. Odile Fenneteau.)
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